Many human diseases such as diabetes, hemophilia, and hepatitis can either be cured or ameliorated by the systemic administration of protein-based pharmaceuticals. Proof-of-principal experiments conducted at Genteric suggest that the salivary glands can be used for this purpose. In order to develop this technology for clinical applications, chemical and formulation parameters will be examined to optimize transgene expression and secretion by the salivary gland. The goal is to enhance the current levels of salivary gland transgene expression to levels that are suitable for clinical development by using cationic lipid technology. The specific aims are to (1) identify the optimal transfection formulation with regard to lipid:DNA ratio, DNA dose, choice of cationic lipid and fraction of co-lipid; (2) evaluate the extent of lipid-associated toxicity on salivary glands by histological examination; (3) quantify the net enhancement in salivary gland secretions of human insulin and human growth hormonr genes using the most active, least toxic transfection formulation. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE